RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with monoclonal antibody therapy and chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with trastuzumab and vinorelbine works in treating women with locally recurrent or metastatic breast cancer.

10 μg/kg subcutaneously (sc) each day for four days or g-CSF at 5 μg/kg sc each day for four days with GM-CSF 250 μg/m2 sc each day for four days. G-CSF and/or GM- CSF will be self-administered. On the fifth day patients will have two intravenous lines placed in the apheresis area of the Blood Bank and then undergo a 15 litre apheresis collection

Biological: trastuzumab

4 mg/kg intravenously, every 14 days

Drug: vinorelbine ditartrate

Vinorelbine 25 mg/m2 will be administered intravenously, every 14 days

Detailed Description:

OBJECTIVES:

Primary

Determine the efficacy of multiepitope autologous dendritic cell vaccine, trastuzumab (Herceptin^®), and vinorelbine by measuring the change in the largest dimension of metastatic lesions, in women with locally recurrent or metastatic breast cancer that does not overexpress HER2/neu.

Secondary

Determine the ability of this regimen to induce functional antigen-specific T cells in these patients by measuring ex-vivo antigen-specific T-cell activity against peptide-pulsed dendritic cells and tumor targets by tetramer staining and intracellular cytokine assays.

OUTLINE:

Autologous dendritic cell mobilization and harvest: All patients undergo autologous dendritic cell mobilization with filgrastim (G-CSF) and/or sargramostim (GM-CSF) subcutaneously daily for 4 days followed by apheresis. Mobilized peripheral blood is processed for the production of dendritic cells by CD34-positive cell selection. The dendritic cells are expanded and then pulsed with E75 and E90 peptides.

Treatment: Patients receive vinorelbine IV over 6-10 minutes and trastuzumab (Herceptin ^®) IV over 90 minutes on day 1. Patients also receive autologous dendritic cells pulsed with E75 and E90 peptides subcutaneously over 2-5 minutes on day 1*. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *If treatment is given locally, the vaccine therapy will be given at UNC-Chapel Hill the following day.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed breast cancer

Locally recurrent or metastatic disease

HLA-A0201 positive by DNA genotyping

HER2/neu expression at least 1+ by immunohistochemistry of tumor sample

CNS metastases allowed provided on therapy for 3 months and stable

Hormone receptor status:

Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Female

Menopausal status

Not specified

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count > 1,500/mm^3

Platelet count > 100,000/mm^3

Hematocrit > 33%

Hepatic

Transaminases ≤ 3 times upper limit of normal

Bilirubin ≤ 2 times normal

Hepatitis B surface antigen negative

Renal

Creatinine < 2.0 mg/dL

Cardiovascular

Ejection fraction > 45% by MUGA OR

Left ventricular function normal by echocardiogram

No serious cardiac condition that would preclude study participation or compliance

Other

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

HIV negative

No serious medical or psychiatric condition that would preclude study participation or compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

Prior biologic therapy allowed

Chemotherapy

More than 30 days since prior cytotoxic chemotherapy

No other concurrent chemotherapy

Endocrine therapy

More than 30 days since prior hormonal therapy

No concurrent hormonal therapy

No concurrent systemic steroids

Radiotherapy

Not specified

Surgery

Not specified

Other

Concurrent bisphosphonates for bone metastases allowed

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088985

Locations

United States, North Carolina

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill